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Surgical strategy for focal cortical dysplasia based on the analysis of the spike onset and peak zones on magnetoencephalography

Hiroshi Shirozu, Akira Hashizume, Hiroshi Masuda, Akiyoshi Kakita, Hiroshi Otsubo, and Shigeki Kameyama


The aim of this study was to elucidate the surgical strategy for focal cortical dysplasia (FCD) based on the interictal analysis on magnetoencephalography (MEG). For this purpose, the correlation between the spike onset zone (Sp-OZ) and the spike peak zone (Sp-PZ) on MEG was evaluated to clarify the differences in the Sp-OZ and its correlation with Sp-PZ in FCD subtypes to develop an appropriate surgical strategy.


Forty-one FCD patients (n = 17 type I, n = 13 type IIa, and n = 11 type IIb) were included. The Sp-OZ was identified by the summation of gradient magnetic-field topography (GMFT) magnitudes at interictal MEG spike onset, and Sp-PZ was defined as the distribution of the equivalent current dipole (ECD) at spike peak. Correlations between Sp-OZ and Sp-PZ distributions were evaluated and compared with clinical factors and seizure outcomes retrospectively.


Good seizure outcomes (Engel class I) were obtained significantly more often in patients with FCD type IIb (10/11, 90.9%) than those with type IIa (4/13, 30.8%; p = 0.003) and type I (6/17, 35.3%; p = 0.004). The Sp-OZ was significantly smaller (1 or 2 gyri) in type IIb (10, 90.9%) than in type IIa (4, 30.8%; p = 0.003) or type I (9, 53.0%; p = 0.036). Concordant correlations between the Sp-OZ and Sp-PZ were significantly more frequent in type IIb (7, 63.6%) than in type IIa (1, 7.7%; p = 0.015) or type I (1, 5.8%; p = 0.004). Complete resection of the Sp-OZ achieved significantly better seizure outcomes (Engel class I: 9/10, 90%) than incomplete resection (11/31, 35.5%) (p = 0.003). In contrast, complete resection of the Sp-PZ showed no significant difference in good seizure outcomes (9/13, 69.2%) compared with incomplete resection (11/28, 39.3%).


The Sp-OZ detected by MEG using GMFT and its correlation with Sp-PZ were related to FCD subtypes. A discordant distribution between Sp-OZ and Sp-PZ in type I and IIa FCD indicated an extensive epileptogenic zone and a complex epileptic network. Type IIb showed a restricted epileptogenic zone with the smaller Sp-OZ and concordance between Sp-OZ and Sp-PZ. Complete resection of the Sp-OZ provided significantly better seizure outcomes than incomplete resection. Complete resection of the Sp-PZ was not related to seizure outcomes. There was a definite difference in the epileptogenic zone among FCD subtypes; hence, an individual surgical strategy taking into account the correlation between the Sp-OZ and Sp-PZ should be considered.

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Computerized brain-surface voltage topographic mapping for localization of intracranial spikes from electrocorticography

Technical note

Hiroshi Otsubo, Atsushi Shirasawa, Shiro Chitoku, James T. Rutka, Scott B. Wilson, and O. Carter Snead III

✓ The purpose of this paper is to describe the use of computerized brain-surface voltage topographic mapping to localize and identify epileptic discharges recorded on electrocorticographic (ECoG) studies in which a subdural grid was used during intracranial video electroencephalographic (IVEEG) monitoring. The authors studied 12 children who underwent surgery for intractable extrahippocampal epilepsy. Cortical surfaces and subdural grid electrodes were photographed during the initial surgery to create an electrode map that could be superimposed onto a picture of the brain surface. Spikes were selected from ictal discharges recorded at the beginning of clinically confirmed seizures and from interictal discharges seen on ECoG studies during IVEEG recording. A computer program was used to calculate the sequential amplitude of the spikes by using squared interpolation, and they were then superimposed onto the electrode map. Interictal discharges and high-amplitude spike complexes at seizure onset were plotted on the map. This mapping procedure depicted the ictal zone in nine patients and the interictal zone in 12, and proved to be an accurate and useful source of information for planning corrective surgery.

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The role of magnetoencephalography in epilepsy surgery

Zulma S. Tovar-Spinoza, Ayako Ochi, James T. Rutka, Cristina Go, and Hiroshi Otsubo

Epilepsy surgery requires the precise localization of the epileptogenic zone and the anatomical localization of eloquent cortex so that these areas can be preserved during cortical resection. Magnetoencephalography (MEG) is a technique that maps interictal magnetic dipole sources onto MR imaging to produce a magnetic source image. Magneto-encephalographic spike sources can be used to localize the epileptogenic zone and be part of the workup of the patient for epilepsy surgery in conjunction with data derived from an analysis of seizure semiology, scalp video electroencephalography, PET, functional MR imaging, and neuropsychological testing. In addition, magnetoencephalographic spike sources can be linked to neuronavigation platforms for use in the neurosurgical field. Finally, paradigms have been developed so that MEG can be used to identify functional areas of the cerebral cortex including the somatosensory, motor, language, and visual evoked fields.

The authors review the basic principles of MEG and the utility of MEG for presurgical planning as well as intra-operative mapping and discuss future applications of MEG technology.

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Surgical outcomes in children with bottom-of-sulcus dysplasia and drug-resistant epilepsy: a retrospective cohort study

Puneet Jain, Ayako Ochi, Carter McInnis, Hiroshi Otsubo, O. Carter Snead III, George M. Ibrahim, Elizabeth Donner, and Elysa Widjaja


Bottom-of-sulcus dysplasia (BOSD) is challenging to identify radiologically. The aim of this study was to explore seizure outcomes after resective surgery or MR-guided laser interstitial thermal therapy (MRgLITT) in children with BOSD.


Children with radiologically defined BOSD who underwent resective surgery or MRgLITT, with at least 1 year of follow-up were included. Clinical, radiological, neurophysiological, and histological data were extracted from medical records. Invasive video EEG (IVEEG) was used to evaluate the ictal onset zone or motor/language mapping, wherever appropriate. Histology of MRI-visible BOSD, including the overlying and adjacent cortex, was also evaluated.


Forty-one children with BOSD underwent surgical treatment. The lesion was initially overlooked on MRI in 20 patients (48.8%). Of 34 patients who underwent IVEEG and who had available ictal data, the ictal onset zone extended beyond the MRI-visible BOSD in 23 patients (67.6%). Surgical treatment included lesionectomy (24 patients), extended lesionectomy (12 patients), lobectomy (1 patient), and ablation of BOSD (4 patients). The pathology in 37 patients who underwent resection showed focal cortical dysplasia type IIB and type IIA in 21 (53.8%) and 16 patients (41%), respectively. Seizure freedom was achieved in 32 patients (78.1%) after a mean follow-up of 4.3 years.


Seizure outcomes after resective surgery or MRgLITT in children with BOSD were generally favorable. The authors found that the neurophysiological abnormality and pathology often extended beyond the MRI-visible BOSD.

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Steal phenomenon in Sturge-Weber syndrome imitating an ictal electroencephalography change in the contralateral hemisphere: report of 2 cases

Chusak Limotai, Cristina Y. Go, Shiro Baba, Kazuo Okanari, Ayako Ochi, James T. Rutka, O. Carter Snead III, and Hiroshi Otsubo

Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they develop seizures and the seizures prove medically refractory. The authors report on 2 infants (15 and 19 months old) with SWS who underwent scalp video electroencephalography (EEG) and subsequent functional hemispherotomy for intractable partial motor seizures due to extensive left hemispheric angiomatosis. They presented with similar interictal and ictal EEG findings. Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the contralateral hemisphere before the build-up of ictal EEG changes on the lesional hemisphere. The patients became seizure free after hemispherotomy. The ictal contralateral slow waves were not a sign of an ictal hemisphere and may indicate prominent ischemic changes resulting from a steal phenomenon of hemispheric angiomatosis during seizure.

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Cortical dysplastic lesions in children with intractable epilepsy: role of complete resection

Walter J. Hader, Mark Mackay, Hiroshi Otsubo, Shiro Chitoku, Shelly Weiss, Lawrence Becker, O. Carter Snead III, and James T. Rutka

Object. The authors conducted a study to determine seizure-related outcomes in a group of pediatric patients with pathologically proven focal cortical dysplasia (FCD) treated by focal cortical resections and multiple subpial transections (MSTs).

Methods. The authors performed a retrospective review of pediatric patients in whom surgery was conducted to treat medically refractory epilepsy secondary to cortical dysplasia between April 1989 and January 2001. Diagnostic studies included preoperative scalp electroencephalography (EEG), magnetic resonance (MR) imaging, positron emission tomography (PET), and magnetoencephalography (MEG). Intraoperative electrocorticography (ECoG) or extraoperative subdural grid EEG monitoring was performed in all patients. Seizure outcome was classified using the Engel scheme. The authors analyzed nine data points and compared these with seizure outcome, including seizure semiology, MR imaging, PET and MEG data, as well as location of resection, intracranial video-EEG findings, MSTs, postresection ECoG data, and histological findings.

The authors analyzed data obtained in 39 children in whom the follow-up interval after epilepsy surgery was at least 18 months. Patients had suffered epilepsy for a mean of 7.7 years prior to surgical intervention and their mean age at treatment was 9.6 years (range 2 months–18 years). A good seizure-related outcome was demonstrated in 28 patients (72%), including 21 (54%) who were free of seizures (Engel Class I) and seven (18%) in whom seizures were rare (Engel Class II). In 11 patients seizure-related outcome was less favorable, including six (15%) with worthwhile improvement involving some seizures (Engel Class III) and five (13%) with no postoperative seizure improvement (Engel Class IV). There was no significant correlation between seizure outcome and data related to seizure characteristics, MR imaging, PET scanning, MEG, location of resection, intracranial video-EEG, postresection ECoG, and histological findings. Eight (50%) of 16 patients who underwent MSTs in addition to incomplete resection of FCD experienced a good outcome (Engel Class I and II). Twenty (87%) of 23 patients in whom resection of FCD was complete and in whom MSTs were not performed experienced a good seizure outcome (p < 0.05).

Conclusions. Complete resection of FCD results in good seizure outcome in a majority of children. When conducted in conjunction with incomplete cortical resection, MSTs do not improve seizure outcome in patients with FCD. Focal cortical dysplasia located outside of eloquent cortex and complete excision of the lesion are the most important predictors of seizure outcome.

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Multiple subpial transections in the treatment of pediatric epilepsy

Jeffrey P. Blount, Wayne Langburt, Hiroshi Otsubo, Shiro Chitoku, Ayako Ochi, Shelly Weiss, O. Carter Snead, and James T. Rutka

Object. The technique involved in multiple subpial transections (MSTs) allows the surgeon treating patients with epilepsy the capability to make disconnective lesions in epileptogenic regions of eloquent cortex. Although there have been increasing numbers of reports in adults of the efficacy and relative safety of this technique, there are relatively few such reports in children. The authors present their experience in 30 children who underwent MSTs during the surgical management of the seizure disorder.

Methods. Thirty consecutive children who underwent MSTs with or without cortical excision form the basis of this retrospective review. An analysis of neurological adverse effects following MSTs and seizure outcome was performed.

Between 1996 and 2000, MSTs were performed either as stand-alone therapy (four patients) or in conjunction with planned cortical excisions (26 patients). Twenty-three children underwent invasive monitoring after placement of subdural grid electrodes, and in seven intraoperative electrocorticography alone was performed. The mean follow-up period for the group was 3.5 years (minimum 30 months in all cases). All 20 patients in whom MSTs were performed in the primary motor cortex experienced transient hemiparesis (mild in 12 and moderate in eight) lasting up to 6 weeks; however, no patient suffered a permanent motor deficit in the long-term follow-up period. In 26 patients who underwent cortical resections followed by MSTs, 12 (46%) were seizure free (Engel Class I) following surgery. Eleven patients (42%) (Engel Classes II and III) continued to suffer seizures but improvement in seizure control was adequate following surgery. In the 23 patients in whom subdural grids were placed to capture the ictal onset zone by invasive video-electroencephalography, MSTs comprised a mean of 37% of the surgically treated area under the grid.

Conclusions. The results of this series demonstrate that MSTs can be performed with acceptable morbidity in children undergoing epilepsy surgery. The precise role of MSTs in controlling seizure frequency and outcome, especially when combined with planned cortical resections, awaits further study.

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Detection of epileptogenic focus using advanced dynamic statistical parametric mapping with magnetoencephalography in a patient with MRI-negative focal cortical dysplasia type IIB

Won Seok Chang, Midori Nakajima, Ayako Ochi, Elysa Widjaja, James T. Rutka, Ivanna Yau, Shiro Baba, and Hiroshi Otsubo

Advanced dynamic statistical parametric mapping (AdSPM) with magnetoencephalography (MEG) was used to identify MRI-negative epileptogenic lesions in this report. A 15-year-old girl had MRI-negative and pharmacology-resistant focal-onset epilepsy. She experienced two types of seizures. Type I consisted of her arousal from sleep, staring, and a forced head-turning movement to the left, followed by secondary generalization. Type II began with an aura of dizziness followed by staring and postictal headache with fatigue. Scalp video-electroencephalography (EEG) captured two type I seizures originating from the right frontocentral region. MEG showed scattered dipoles over the right frontal region. AdSPM identified the spike source at the bottom of the right inferior frontal sulcus. Intracranial video-EEG captured one type I seizure, which originated from the depth electrode at the bottom of the sulcus and correlated with the AdSPM spike source. Accordingly, the patient underwent resection of the middle and inferior frontal gyri, including the AdSPM-identified spike source. Histopathological examination revealed that the patient had focal cortical dysplasia type IIB. To date, the patient has been seizure free for 2 years while receiving topiramate treatment. This is the first preliminary report to identify MRI-negative epilepsy using AdSPM. Further investigation of AdSPM would be valuable for cases of MRI-negative focal epilepsy.

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Intracranial germ-cell tumors in children

Harold J. Hoffman, Hiroshi Otsubo, E. Bruce Hendrick, Robin P. Humphreys, James M. Drake, Laurence E. Becker, Mark Greenberg, and Derek Jenkin

✓ All patients with confirmed intracranial germ-cell tumors treated at the Hospital of Sick Children during the period January, 1952, to December, 1989, were reviewed. Of the 51 tumors reviewed, 16 were located in the suprasellar region, 32 in the pineal region, and three in both the pineal and the suprasellar regions. Forty-nine patients underwent surgical resection which was total in seven and partial in 20, and consisted of a biopsy in 22. Two patients were managed on the basis of serum and cerebrospinal fluid markers. Surgical tools such as the operating microscope, the ultrasonic surgical aspirator, and the laser beam allowed safe debulking and removal of the deep-seated tumors in the pineal region. There were no operative deaths in the 36 patients treated since 1972, who included 23 with pineal tumors. Twenty-five patients with germinomas received radiotherapy and had a 5-year survival rate of 85.1%. Thirteen patients with non-germinoma germ-cell tumors received radiotherapy and had a 5-year survival rate of 45.5%. On the basis of this review, the authors recommend resection of pineal and suprasellar germ-cell tumors in order to firmly establish an accurate histological diagnosis to guide the extent of adjuvant therapy. In the case of a pure germinoma without evidence of dissemination, adjuvant therapy consists only of local radiotherapy. On the other hand, for malignant non-germinoma germ-cell tumors, adjuvant therapy must include chemotherapy as well as craniospinal axis radiotherapy.

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Pathology of temporal lobectomy for refractory seizures in children

Review of 20 cases including some unique malformative lesions

Venita Jay, Laurence E. Becker, Hiroshi Otsubo, Paul A. Hwang, Harold J. Hoffman, and Derek Harwood-Nash

✓ Significant pathological abnormalities were encountered in a series of 20 temporal lobectomies in children with intractable complex partial seizures. In particular, “dual pathology” (mesial temporal sclerosis with other lesions) was found rather than mesial temporal sclerosis as the only lesion. Unusual pathological findings included capillary penetration of neurons in a neuronal heterotopia in one patient, and foci of extensive cortical disorganization in some cases of mixed tumors and gangliogliomas. A high proportion of neuronal migration disorders was also seen with overlapping pathological features between cortical dysplasia and tuberous sclerosis. In this correlative clinical, radiological, electroencephalographic, and pathological study, some of the pathological lesions in children did not fit the classical categories of neoplasia and malformation and transitional forms were rarely encountered.